study of ha121-28 in patients with non-small cell lung cancer

Conditions: NSCLC

Summary: this study is a multicenter, open-label, single-arm phase ii study to evaluate efficacy and safety of ha121-28 tablets in patients with rearranged during transfection (ret) fusion-positive advanced non-small cell lung cancer (nsclc).


Eligibility criteria:
inclusion criteria: 1. voluntarily participate in this study and sign the informed consent form; 2. aged 18 \~ 75 years old (inclusive), male or female; 3. patients with histologically or cytologically confirmed unresectable locally advanced or metastatic non-small cell lung cancer; 4. ret gene fusion, as demonstrated by "next-generation" sequencing(ngs) method in central laboratory with college of american pathologists(cap) or clinical laboratory improvement amendments(clia) certification; 5. progressive disease after at least one line of standard therapy (including patients with disease progression during or within 6 months of the end of adjuvant therapy); 6. at least one measurable lesion according to recist 1.1 (for lesions previously treated with radiation, the lesion can be included as a measurable lesion only if there is clear disease progression after radiotherapy); 7. eastern cooperative oncology group (ecog) performance status (ps) score 0-1; 8. adequate organ function, laboratory tests meeting the following criteria: * neutrophil count (anc) ≥ 1.5 × 10\^9/l (no g-csf for wbc-elevating therapy within 2 weeks prior to the laboratory test); * platelet count (plt) ≥ 75 × 10\^9/l (no platelet transfusion or other drugs to promote platelet production within 2 weeks prior to the laboratory test); * hemoglobin (hb) ≥ 90 g/l; (not receiving red blood cell transfusion or erythropoiesis-stimulating drugs within 2 weeks prior to the laboratory test); * alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 3 × upper limit of normal (uln) (≤ 5.0 × uln for patients with liver metastases); * serum total bilirubin (tbil) ≤ 1.5 × uln; * serum creatinine ≤ 1.5 × uln; * albumin ≥ 30 g/l; 9. male and female patients of childbearing age agree to take effective contraceptive measures during treatment and within 6 months after the completion of treatment. exclusion criteria: 1. had a documented oncogenic driver gene alteration other than ret in nsclc, ie, activating egfr, braf, or kras mutation, met exon 14 skipping mutation or high-level amplification, and alk, ros1, or ntrk1/2/3 gene fusions; 2. prior treatment with selective ret inhibitors (including investigational selective ret inhibitors, such as loxo-292, blu-667, rxdx-105, etc.); 3. patients who previously received any anti-tumor therapy (including but not limited to chemotherapy, radiotherapy and targeted therapy, etc.) within 4 weeks before the first use of the study drug; traditional chinese medicine or chinese patent medicine with anti-tumor indications within 2 weeks; local palliative radiotherapy for the relief of bone metastasis pain within 2 weeks; 4. abnormal coagulation function (inr \> 1.5 or aptt \> 1.5 × uln); patients with bleeding tendency (such as active peptic ulcer) or receiving thrombolytic or anticoagulant therapy; 5. urine routine showed urine protein ≥ + + and 24 h urine protein \> 1.0 g; 6. patients who have undergone major surgical procedures within 4 weeks before the first dose or are expected to undergo major surgery during the study; 7. patients with central nervous system (cns) metastases who present with progressive neurological symptoms or require an increase in corticosteroid dose to control their cns disease. if a patient requires treatment with corticosteroids for cns disease, the dose must be stable for two weeks prior to the first dose; 8. presence of poorly controlled pericardial, pleural, or peritoneal effusion; 9. interstitial pneumonia requiring steroid therapy, drug-induced pneumonitis, radiation pneumonitis (except for stable radiation pneumonitis); 10. significant cardiovascular disease, such as heart failure greater than new york heart association (nyha) class 2, unstable angina, serious arrhythmia, myocardial infarction or stroke within 6 months prior to the first dose, poorly controlled hypertension (defined as systolic blood pressure \> 150 mmhg or diastolic blood pressure \> 100 mmhg on multiple measurements while on medication); 11. patients who met any of the following criteria will be excluded: * qt interval (qtcf) value ≥ 470 ms for females and ≥ 450 ms for males; or congenital long qt syndrome, taking drugs known to prolong qt interval, family history of long qt syndrome; * resting ecg showed any clinically significant abnormalities in rhythm, conduction, or morphology that required clinical intervention; * cardiac ejection fraction less than 50%; 12. patients with active hepatitis b virus or hepatitis c virus infection: * hbsag positive with hbv dna higher than the upper limit of normal range of the study site; * hcv antibody positive with hcv rna higher than upper limit of normal range of the site; 13. human immunodeficiency virus infected (hiv positive); 14. inability or severe dysphagia; 15. patients who have suffered from or are complicated with any other malignant tumor within 5 years (except radically resected skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate cancer, in situ cervical cancer or other carcinoma in situ); 16. presence of any severe and/or uncontrolled disease that may affect the drug evaluation in the judgment of the investigator, including but not limited to: life-threatening autoimmune system diseases; drug abuse; severe nervous system diseases (such as epilepsy, dementia, etc.); history of severe mental disorders; severe infection, etc.; 17. pregnant or lactating women; 18. other conditions that, in the opinion of the investigator, make participation in the study unsuitable.